The major objective of our studies is to characterize cell surface structures on T lymphocytes which, in addition to the antigen specific receptor (Ti), are involved in the process of lymphocyte activation. We have defined the Thy-1 antigen as one of the critical signal transducing molecules in murine lymphoid cells. Transfection studies of the murine Thy-1.2 gene into the human T cell Jurkat have demonstrated that Thy-1 mediated T cell activation requires co-expression of the CD3 (T3)/Ti complex. We have combined studies using monoclonal antibodies (mAbs) with biochemical and molecular studies of T cell receptor (TCR) gene expression and demonstrated that Thy-1+ dendritic epidermal cells (Thy-1+ DEC), a unique population of cells within the murine epidermis, express the CD3 complex in associated with the products of the TCR gamma- and delta-chain genes. Lastly, we have developed a rapid, quantitative model for the assessment of a number of parameters of lymphocyte activation in vivo. We have used this assay system to examine the effects of the immunosuppressive drug, Cyclosporin A (Cy A), on the development of lymphocyte activation in vivo and demonstrated that mechanism of action of Cy A in vivo may be distinct from its mechanism of action in vitro.